Divergence of mammalian higher order chromatin structure is associated with developmental loci.

Several recent studies have examined different aspects of mammalian higher order chromatin structure - replication timing, lamina association and Hi-C inter-locus interactions - and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of...

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Main Authors: Emily V Chambers, Wendy A Bickmore, Colin A Semple
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-04-01
Series:PLoS Computational Biology
Online Access:http://europepmc.org/articles/PMC3617018?pdf=render
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author Emily V Chambers
Wendy A Bickmore
Colin A Semple
author_facet Emily V Chambers
Wendy A Bickmore
Colin A Semple
author_sort Emily V Chambers
collection DOAJ
description Several recent studies have examined different aspects of mammalian higher order chromatin structure - replication timing, lamina association and Hi-C inter-locus interactions - and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution.
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spelling doaj.art-bc3a9f4fcb9049dba98f5c6edf317d122022-12-22T03:43:56ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582013-04-0194e100301710.1371/journal.pcbi.1003017Divergence of mammalian higher order chromatin structure is associated with developmental loci.Emily V ChambersWendy A BickmoreColin A SempleSeveral recent studies have examined different aspects of mammalian higher order chromatin structure - replication timing, lamina association and Hi-C inter-locus interactions - and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution.http://europepmc.org/articles/PMC3617018?pdf=render
spellingShingle Emily V Chambers
Wendy A Bickmore
Colin A Semple
Divergence of mammalian higher order chromatin structure is associated with developmental loci.
PLoS Computational Biology
title Divergence of mammalian higher order chromatin structure is associated with developmental loci.
title_full Divergence of mammalian higher order chromatin structure is associated with developmental loci.
title_fullStr Divergence of mammalian higher order chromatin structure is associated with developmental loci.
title_full_unstemmed Divergence of mammalian higher order chromatin structure is associated with developmental loci.
title_short Divergence of mammalian higher order chromatin structure is associated with developmental loci.
title_sort divergence of mammalian higher order chromatin structure is associated with developmental loci
url http://europepmc.org/articles/PMC3617018?pdf=render
work_keys_str_mv AT emilyvchambers divergenceofmammalianhigherorderchromatinstructureisassociatedwithdevelopmentalloci
AT wendyabickmore divergenceofmammalianhigherorderchromatinstructureisassociatedwithdevelopmentalloci
AT colinasemple divergenceofmammalianhigherorderchromatinstructureisassociatedwithdevelopmentalloci